Can fluvoxamine cause liver damage? (+5 factors)

In this article, we will discuss the liver damage caused by fluvoxamine, as well as the risk factors, symptoms, and management of fluvoxamine-induced liver damage.

Can fluvoxamine cause liver damage?

Yes, fluvoxamine can cause liver damage. However, the intensity and frequency of fluvoxamine-induced liver damage varies from one individual to another based on individual sensitivity to the medication and underlying risk factors.

Fluvoxamine is a selective serotonin reuptake inhibitor antidepressant medication. It increases the levels of serotonin and to a lesser extent dopamine in the brain.  It is most frequently prescribed to manage and treat various mental disorders such as deression, anxiety, and obsessive-compulsive disorder, especially in children. Fluvoxamine is metabolized by CYP450 liver enzymes via oxidation.

The metabolites formed in the liver are pharmacologically inactive and are excreted through the kidneys in urine (1).

How can fluvoxamine cause liver damage?

The mechanism by which fluvoxamine may cause liver damage is linked to its metabolism and the increased burden on the liver. Fluvoxamine undergoes extensive hepatic metabolism, primarily through the CYP450 enzyme system, specifically CYP1A2 and CYP2D6 (5).

This metabolic process generates various metabolites, some of which may have toxic effects on liver cells. The accumulation of these metabolites, along with the drug’s extended half-life, could lead to an increased burden on the liver, potentially contributing to hepatotoxicity.

Some cases of fluvoxamine-induced liver injury may involve an immune response. The body’s immune system may recognize the drug or its metabolites as foreign substances, leading to an inflammatory response that damages liver cells (2).

What does research suggest?

According to research, fluvoxamine is prone to increase the levels of several liver enzymes such as aminotransferase. The elevated levels of these enzymes are linked with significant liver damage caused by fluvoxamine (2). 

A research study reported the incidence of hepatitis in individuals who were taking fluvoxamine to manage the symptoms of their underlying depression disorders (3).

Research studies show that fluvoxamine can cause liver damage, but the intensity varies based on individual sensitivity. It increases liver enzymes, and hepatic test abnormalities occur in less than 1% of patients. Symptoms of liver damage are not specific in these individuals, and there is no specific treatment for fluvoxamine-induced hepatotoxicity. However, in some cases, discontinuation of the medication is required (2).

Research suggested that discontinuation of several antidepressant medications including fluvoxamine, sertraline, and mirtazapine is associated with inducing hepatic damage which is reversible in nature. The hepatic damage occurred in individuals with fluvoxamine irrespective of the presence of any risk factor (4).

Factors increasing the risk of liver damage while taking fluvoxamine

The risk of fluvoxamine-induced liver damage is increased in some individuals due to the presence of certain risk factors, including:

  • underlying liver diseases such as hepatitis, cirrhosis, jaundice, etc
  • use of alcohol
  • concurrent use of hepatotoxic medications including ciprofloxacin, paracetamol, and isoniazid
  • concurrent use of medications that inhibit CYP450 liver enzymes that metabolize fluvoxamine
  • obesity

However, different studies have reported the occurrence of liver damage in individuals without any risk factors. Individual sensitivity to fluvoxamine can also play an important role in the induction of fluvoxamine-induced hepatotoxicity as well as other side effects of this medication.

How to reduce the risks of liver damage while taking fluvoxamine?

Minimizing the risk of liver damage while taking fluvoxamine involves several precautionary measures and regular monitoring. Here are some tips to reduce the risks of fluvoxamine-induced liver damage:

Healthy lifestyle: The risk of liver damage can be reduced by maintaining a healthy lifestyle which includes eating a balanced and nutritious diet and limiting the intake of fatty food. Proper hydration with an adequate amount of water supports overall hepatic function and helps remove toxins from the body.

Reduce weight: Maintain your weight through a combination of a balanced diet and regular exercise. Obesity is linked to fatty liver disease, which can progress to more severe liver conditions.

Physical activity: Regular physical exercise not only promotes overall health but also helps in the management of weight, which reduces the risk of liver-related issues. 

Avoid alcohol: Preventing alcohol-related exacerbation of liver damage while taking fluvoxamine involves complete abstinence from alcohol, seeking medical advice for any existing liver conditions, and adopting a healthy lifestyle.

Regular monitoring: Conduct routine liver function tests before starting fluvoxamine and throughout treatment. This helps detect any early signs of liver damage.

Medication review: Adjust the dosage of fluvoxamine based on individual patient characteristics, including liver function, and avoid concurrent use of other medications that can cause liver damage.

What are the symptoms of fluvoxamine-induced liver damage?

The most common symptoms associated with the liver damage caused by fluvoxamine are:

  • elevated liver enzymes
  • jaundice
  • vomiting
  • abdominal pain
  • hepatitis
  • fatigue
  • weight loss
  • skin itching

However, the frequency and intensity of these symptoms may vary from one individual to another based on their individual sensitivity to fluvoxamine and overall health condition. There are no specific symptoms of fluvoxamine-induced liver damage that occur in all the individuals taking fluvoxamine (2).

How to manage fluvoxamine-induced liver damage?

If you experience any symptoms of liver damage after taking fluvoxamine, report them to your healthcare provider as soon as possible. They will determine the exact cause of your liver damage and guide you based on your specific condition.

If liver damage is associated with fluvoxamine, your healthcare provider may adjust the dosage of fluvoxamine or if necessary recommend an alternative to fluvoxamine. However, it is important to note that you should never stop taking fluvoxamine without consultation with your doctor. Sudden discontinuation of fluvoxamine may lead to withdrawal effects.

Regularly monitor the liver functions if you are taking fluvoxamine with pre-existing liver diseases such as jaundice, hepatitis, or liver cirrhosis. Do not miss any appointments with your healthcare provider to prevent further liver damage. 

Conclusion

In my opinion, based on my knowledge and experience,  SSRI antidepressants including fluvoxamine are associated with liver damage. The extent and severity of liver damage caused by fluvoxamine may vary from one individual to another based on their overall health and underlying medical condition. However, the presence of existing liver diseases increases the risk of fluvoxamine-induced hepatotoxicity.

It is advisable to discuss your underlying medical conditions including liver disease and the concurrent medications with your healthcare provider before starting fluvoxamine so they can adjust the treatment plan according to your individual needs.

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References

1.-

van Harten J. Overview of the pharmacokinetics of fluvoxamine. Clin Pharmacokinet. 1995;29 Suppl 1:1-9. doi: 10.2165/00003088-199500291-00003. PMID: 8846617. https://pubmed.ncbi.nlm.nih.gov/8846617/

2.-

LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Fluvoxamine. [Updated 2021 May 11]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548905/

3.-

Lam KS, Blanchi A, Chavaillon JM. Hépatite probablement secondaire à la prise massive de fluvoxamine [Hepatitis probably secondary to the massive ingestion of fluvoxamine]. Gastroenterol Clin Biol. 1988 Apr;12(4):398-9. French. PMID: 3133277. https://pubmed.ncbi.nlm.nih.gov/3133277/

4.-

Park, Susie & Ishino, Risa. (2013). Liver Injury Associated with Antidepressants. Current drug safety. 8. 207-23. 10.2174/1574886311308030011. https://www.researchgate.net/publication/255692499

5.-

van Harten J. Overview of the pharmacokinetics of fluvoxamine. Clin Pharmacokinet. 1995;29 Suppl 1:1-9. doi: 10.2165/00003088-199500291-00003. PMID: 8846617. https://pubmed.ncbi.nlm.nih.gov/8846617

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